期刊
NATURE
卷 464, 期 7291, 页码 1062-U135出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature08978
关键词
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资金
- National Institutes of Health [CA136837]
- Department of Defense [W81XWH-06-1-0362]
Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces(1,2), and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis(3-6). Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.
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